Wu Siyuan, Wang Gaochao, Gu Likai, Zhang Yinjie, Wang Zhihuai
Nanjing Medical University, Nanjing, 211166, China; The Department of Hepato-biliary-pancreatic Surgery, The Institute of Hepatobiliary and Pancreatic Diseases, The Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou, China.
Nanjing Medical University, Nanjing, 211166, China; The Department of Hepato-biliary-pancreatic Surgery, The Institute of Hepatobiliary and Pancreatic Diseases, The Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou, China.
Transl Oncol. 2025 Jan;51:102189. doi: 10.1016/j.tranon.2024.102189. Epub 2024 Nov 14.
The study highlights that RPS21, a gene encoding a component of the 40S ribosomal subunit, plays an oncogenic role in hepatocellular carcinoma (HCC) and may influence tumor aggressiveness by affecting antioxidant capacity. RPS21 was found to be upregulated in HCC through RNA-sequencing of clinical samples and analysis of the TCGA database. Kaplan-Meier survival analyses linked higher RPS21 expression to lower survival rates across multiple metrics (OS, PFS, RFS, DSS). Mutation analysis via the cBioPortal showed that primarily amplifications in RPS21 are associated with a poorer prognosis. Tissue microarrays confirmed higher RPS21 levels in tumor samples, which were associated with more advanced clinical stages and grades. Experimental interventions involving lentiviral knockdown or overexpression of RPS21 significantly altered HCC cell proliferation and migration. These findings were supported by mouse models, which showed impacts on tumor growth and metastasis. Further mechanistic studies indicated that RPS21 modulates the ubiquitination and stability of GPX4, a key player in ferroptosis and oxidative stress regulation in HCC cells. This comprehensive study, which merges bioinformatic analysis with laboratory research, positions RPS21 as a viable target for HCC therapy and opens new pathways for understanding and treating liver cancer.
该研究强调，编码40S核糖体亚基组成部分的基因RPS21在肝细胞癌（HCC）中发挥致癌作用，并可能通过影响抗氧化能力来影响肿瘤侵袭性。通过对临床样本的RNA测序和TCGA数据库分析，发现RPS21在HCC中上调。Kaplan-Meier生存分析表明，较高的RPS21表达与多个指标（总生存期、无进展生存期、无复发生存期、疾病特异性生存期）的较低生存率相关。通过cBioPortal进行的突变分析表明，RPS21的主要扩增与较差的预后相关。组织芯片证实肿瘤样本中RPS21水平较高，这与更晚期的临床分期和分级相关。涉及慢病毒敲低或过表达RPS21的实验干预显著改变了HCC细胞的增殖和迁移。这些发现得到了小鼠模型的支持，该模型显示了对肿瘤生长和转移的影响。进一步的机制研究表明，RPS21调节GPX4的泛素化和稳定性，GPX4是HCC细胞中铁死亡和氧化应激调节的关键因子。这项将生物信息学分析与实验室研究相结合的综合研究，将RPS21定位为HCC治疗的可行靶点，并为理解和治疗肝癌开辟了新途径。
